tbuckley/cabot-search huggingface dataset:
MAIT and Vδ2 unconventional T cells are supported by a diverse intestinal microbiome and correlate with favorable patient outcome after allogeneic HCT
Authors: Hana Andrlová, Oriana Miltiadous, Anastasia I. Kousa, Anqi Dai, Susan DeWolf, Sara Violante, Hee-Yon Park, Sudha Janaki-Raman, Rui Gardner, Sary El Daker, John Slingerland, Paul Giardina, Annelie Clurman, Antonio L. C. Gomes, Chi Nguyen, Marina Burgos da Silva, Gabriel K. Armijo, Nicole Lee, Roberta Zappasodi, Ronan Chaligne, Ignas Masilionis, Emily Fontana, Doris Ponce, Christina Cho, Amy Bush, Lauren Hill, Nelson Chao, Anthony D. Sung, Sergio Giralt, Esther H. Vidal, Kinga K. Hosszu, Sean M. Devlin, Jonathan U. Peled, Justin R. Cross, Miguel-Angel Perales, Dale I. Godfrey, Marcel R. M. van den Brink, Kate A. Markey
Journal: Science Translational Medicine (2022)

Microbial diversity is associated with improved outcomes in recipients of allogeneic hematopoietic cell transplantation (allo-HCT), but the mechanism underlying this observation is unclear. In a cohort of 174 patients who underwent allo-HCT, we demonstrate that a diverse intestinal microbiome early after allo-HCT is associated with an increased number of innate-like mucosal-associated invariant T (MAIT) cells, which are in turn associated with improved overall survival and less acute graft-versus-host disease (aGVHD). Immune profiling of conventional and unconventional immune cell subsets revealed that the prevalence of Vδ2 cells, the major circulating subpopulation of γδ T cells, closely correlated with the frequency of MAIT cells and was associated with less aGVHD. Analysis of these populations using both single-cell transcriptomics and flow cytometry suggested a shift toward activated phenotypes and a gain of cytotoxic and effector functions after transplantation. A diverse intestinal microbiome with the capacity to produce activating ligands for MAIT and Vδ2 cells appeared to be necessary for the maintenance of these populations after allo-HCT. These data suggest an immunological link between intestinal microbial diversity, microbe-derived ligands, and maintenance of unconventional T cells.
Glucose-Dependent Insulinotropic Polypeptide—A Postprandial Hormone with Unharnessed Metabolic Potential
Authors: Nunzio Guccio, Fiona M. Gribble, Frank Reimann
Journal: Annual Review of Nutrition (2022)

Glucose-dependent insulinotropic polypeptide (GIP) is released from the upper small intestine in response to food intake and contributes to the postprandial control of nutrient disposition, including of sugars and fats. Long neglected as a potential therapeutic target, the GIPR axis has received increasing interest recently, with the emerging data demonstrating the metabolically favorable outcomes of adding GIPR agonism to GLP-1 receptor agonists in people with type 2 diabetes and obesity. This review examines the physiology of the GIP axis, from the mechanisms underlying GIP secretion from the intestine to its action on target tissues and therapeutic development.
Socioeconomic disadvantage contributes to ethnic disparities in multiple myeloma survival: a matched cohort study
Authors: Christopher Staffi Buradagunta, Zhuping Garacci, Anita D’Souza, Binod Dhakal, Sumana Devata, Siegfried Janz, Aaron P. Thrift, Parameswaran Hari, Melinda Stolley, Jing Dong
Journal: Blood Cancer Journal (2022)
COVID-19 vaccine effectiveness against the omicron (BA.2) variant in England
Authors: Freja C M Kirsebom, Nick Andrews, Julia Stowe, Samuel Toffa, Ruchira Sachdeva, Eileen Gallagher, Natalie Groves, Anne-Marie O'Connell, Meera Chand, Mary Ramsay, Jamie Lopez Bernal
Journal: The Lancet Infectious Diseases (2022)
Targeting Adiponectin Receptor 1 Phosphorylation Against Ischemic Heart Failure
Authors: Di Zhu, Zhen Zhang, Jianli Zhao, Demin Liu, Lu Gan, Wayne Bond Lau, Dina Xie, Zhijun Meng, Peng Yao, Jumpei Tsukuda, Theodore A. Christopher, Bernard L. Lopez, Erhe Gao, Walter J. Koch, Yajing Wang, Xin-Liang Ma
Journal: Circulation Research (2022)

Background: Despite significantly reduced acute myocardial infarction (MI) mortality in recent years, ischemic heart failure continues to escalate. Therapeutic interventions effectively reversing pathological remodeling are an urgent unmet medical need. We recently demonstrated that AdipoR1 (APN [adiponectin] receptor 1) phosphorylation by GRK2 (G-protein–coupled receptor kinase 2) contributes to maladaptive remodeling in the ischemic heart. The current study clarified the underlying mechanisms leading to AdipoR1 phosphorylative desensitization and investigated whether blocking AdipoR1 phosphorylation may restore its protective signaling, reversing post-MI remodeling. Methods: Specific sites and underlying molecular mechanisms responsible for AdipoR1 phosphorylative desensitization were investigated in vitro (neonatal and adult cardiomyocytes). The effects of AdipoR1 phosphorylation inhibition upon APN post-MI remodeling and heart failure progression were investigated in vivo. Results: Among 4 previously identified sites sensitive to GRK2 phosphorylation, alanine substitution of Ser 205 (AdipoR1 S205A ), but not other 3 sites, rescued GRK2-suppressed AdipoR1 functions, restoring APN-induced cell salvage kinase activation and reducing oxidative cell death. The molecular investigation followed by functional determination demonstrated that AdipoR1 phosphorylation promoted clathrin-dependent (not caveolae) endocytosis and lysosomal-mediated (not proteasome) degradation, reducing AdipoR1 protein level and suppressing AdipoR1-mediated cytoprotective action. GRK2-induced AdipoR1 endocytosis and degradation were blocked by AdipoR1 S205A overexpression. Moreover, AdipoR1 S205E (pseudophosphorylation) phenocopied GRK2 effects, promoted AdipoR1 endocytosis and degradation, and inhibited AdipoR1 biological function. Most importantly, AdipoR1 function was preserved during heart failure development in AdipoR1-KO (AdipoR1 knockout) mice reexpressing hAdipoR1 S205A . APN administration in the failing heart reversed post-MI remodeling and improved cardiac function. However, reexpressing hAdipoR1 WT in AdipoR1-KO mice failed to restore APN cardioprotection. Conclusions: Ser 205 is responsible for AdipoR1 phosphorylative desensitization in the failing heart. Blockade of AdipoR1 phosphorylation followed by pharmacological APN administration is a novel therapy effective in reversing post-MI remodeling and mitigating heart failure progression.
Clinician Shortage Exacerbates Pandemic-Fueled “Mental Health Crisis”
Authors: Bridget M. Kuehn
Journal: JAMA (2022)

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Defining the key intrahepatic gene networks in HCV infection driven by sex
Authors: Emanuele Marchi, Narayan Ramamurthy, M Azim Ansari, Caroline E Harrer, Eleanor Barnes, Paul Klenerman
Journal: Gut (2022)

Objective The transcriptional response in the liver during HCV infection is critical for determining clinical outcomes. This issue remains relatively unexplored as tissue access to address this at scale is usually limited. We aimed to profile the transcriptomics of HCV-infected livers to describe the expression networks involved and assess the effect on them of major predictors of clinical outcome such as IFNL4 (interferon lambda 4) host genotype and sex. Design We took advantage of a large clinical study of HCV therapy accompanied by baseline liver biopsy to examine the drivers of transcription in tissue samples in 195 patients also genotyped genome-wide for host and viral single nucleotide polymorphisms. We addressed the role of host factors (disease status, sex, genotype, age) and viral factors (load, mutation) on transcriptional responses. Results We observe key modules of transcription which can be impacted differentially by host and viral factors. Underlying cirrhotic state had the most substantial impact, even in a stable, compensated population. Notably, sex had a major impact on antiviral responses in concert with IL28B (interleukin 28B)/IFNL4 genotype, with stronger interferon and humoral responses in females. Males tended towards a dominant cellular immune response. In both sexes, there was a strong influence of the underlying host disease status and of specific viral mutations, and sex-specific expression quantitative trait loci were also observed. Conclusion These features help define the major influences on tissue responses in HCV infection, impacting on the response to treatment and with broader implications for responses in other sex-biased infections.
Mn<sup>2+</sup>/Fe<sup>3+</sup>/Co<sup>2+</sup> and Tetrasulfide Bond Co‐Incorporated Dendritic Mesoporous Organosilica as Multifunctional Nanocarriers: One‐Step Synthesis and Applications for Cancer Therapy
Authors: Bin Liu, Lili Feng, Yulong Bian, Meng Yuan, Yanlin Zhu, Piaoping Yang, Ziyong Cheng, Jun Lin
Journal: Advanced Healthcare Materials (2022)

Abstract Enriching the application of multifunctional dendritic mesoporous organosilica (DMOS) is still challenging in anti‐cancer research. Herein, manganese ions, iron ions, or cobalt ions and tetrasulfide bonds are co‐incorporated into the framework of DMOS to yield multifunctional nanoparticles denoted as Mn‐DMOS, Fe‐DMOS, or Co‐DMOS by directly doping metal ions during the synthetic process. Due to co‐incorporation of metal ions and tetrasulfide bonds, these designed nanocarriers have more functions rather than only for cargo delivery. As proof of concept, the nanocomposite is established based on Mn‐DMOS as an efficient nanocarrier for indocyanine green (ICG) delivery and modification with polyethylene glycol. In the tumor microenvironment, the generated hydrogen sulfide (H 2 S) arising from the reaction between tetrasulfide bond and over‐expressed glutathione (GSH) causes mitochondrial injury to reduce cellular respiration. The released Mn 2+ from the rapidly decomposed nanocomposite catalyzes the endogenous hydrogen peroxide to produce oxygen (O 2 ). The photothermal effect from the released ICG initiated by the near‐infrared light induces cancer cells apoptosis and simultaneously enhances the content of blood O 2 at tumor sites. Therefore, due to the GSH depletion and trimodal O 2 compensation, the photodynamic therapy efficiency of ICG has significantly improved. In brief, these designed nanocarriers will play advanced roles in cancer therapy.
IL-20 subfamily cytokines impair the oesophageal epithelial barrier by diminishing filaggrin in eosinophilic oesophagitis
Authors: Tanay Kaymak, Berna Kaya, Philipp Wuggenig, Sandro Nuciforo, Andreas Göldi, Franz Oswald, Julien Roux, Mario Noti, Hassan Melhem, Petr Hruz, Jan Hendrik Niess
Journal: Gut (2022)

Objective Disruption of the epithelial barrier plays an essential role in developing eosinophilic oesophagitis (EoE), a disease defined by type 2 helper T cell (Th2)-mediated food-associated and aeroallergen-associated chronic inflammation. Although an increased expression of interleukin (IL)-20 subfamily members, IL-19, IL-20 and IL-24, in Th2-mediated diseases has been reported, their function in EoE remains unknown. Design Combining transcriptomic, proteomic and functional analyses, we studied the importance of the IL-20 subfamily for EoE using patient-derived oesophageal three-dimensional models and an EoE mouse model. Results Patients with active EoE have increased expression of IL-20 subfamily cytokines in the oesophagus and serum. In patient-derived oesophageal organoids stimulated with IL-20 cytokines, RNA sequencing and mass spectrometry revealed a downregulation of genes and proteins forming the cornified envelope, including filaggrins. On the contrary, abrogation of IL-20 subfamily signalling in Il20R2 −/− animals resulted in attenuated experimental EoE reflected by reduced eosinophil infiltration, lower Th2 cytokine expression and preserved expression of filaggrins in the oesophagus. Mechanistically, these observations were mediated by the mitogen-activated protein kinase (MAPK); extracellular-signal regulated kinases (ERK)1/2) pathway. Its blockade prevented epithelial barrier impairment in patient-derived air–liquid interface cultures stimulated with IL-20 cytokines and attenuated experimental EoE in mice. Conclusion Our findings reveal a previously unknown regulatory role of the IL-20 subfamily for oesophageal barrier function in the context of EoE. We propose that aberrant IL-20 subfamily signalling disturbs the oesophageal epithelial barrier integrity and promotes EoE development. Our study suggests that specific targeting of the IL-20 subfamily signalling pathway may present a novel strategy for the treatment of EoE.
Efficacy of Combined <i>Abelmoschus manihot</i> and Irbesartan for Reduction of Albuminuria in Patients With Type 2 Diabetes and Diabetic Kidney Disease: A Multicenter Randomized Double-Blind Parallel Controlled Clinical Trial
Authors: Jing Zhao, Isabelle Tostivint, Lingdong Xu, Jihan Huang, Laetitia Gambotti, Jean-Jacques Boffa, Min Yang, Ling Wang, Zhuxing Sun, Xiaolan Chen, Amélie Liou-Schischmanoff, Alain Baumelou, Teng Ma, Guoyuan Lu, Ling Li, Dai Chen, Laurence Piéroni, Bingkai Liu, Xiao Qin, Weiming He, Yuejuan Wang, Harvest F. Gu, Wei Sun
Journal: Diabetes Care (2022)
PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism
Authors: Mingming Sun, Leilei Li, Yujia Niu, Yingzhi Wang, Qi Yan, Fei Xie, Yaya Qiao, Jiaqi Song, Huanran Sun, Zhen Li, Sizhen Lai, Hongkai Chang, Han Zhang, Jiyan Wang, Chenxin Yang, Huifang Zhao, Junzhen Tan, Yanping Li, Shuangping Liu, Bin Lu, Min Liu, Guangyao Kong, Yujun Zhao, Chunze Zhang, Shu-Hai Lin, Cheng Luo, Shuai Zhang, Changliang Shan
Journal: Acta Pharmaceutica Sinica B (2022)

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
Retraction notice to “Intramuscular delivery of 3D aggregates of HUVECs and cbMSCs for cellular cardiomyoplasty in rats with myocardial infarction” [Journal of Controlled Release 172 (2013) 419–425]
Authors: Ding-Yuan Chen, Hao-Ji Wei, Wei-Wen Lin, Kun-Ju Lin, Chieh-Cheng Huang, Cheng-Tse Wu, Shiaw-Min Hwang, Yen Chang, Hsing-Wen Sung
Journal: Journal of Controlled Release (2022)
Noninvasive biomarkers for the diagnosis and management of autoimmune hepatitis
Authors: Claire Harrington, Swathi Krishnan, Cara L. Mack, Paolo Cravedi, David N. Assis, Josh Levitsky
Journal: Hepatology (2022)

Autoimmune hepatitis (AIH) is a rare disease of unclear etiology characterized by loss of self-tolerance that can lead to liver injury, cirrhosis, and acute liver failure. First-line treatment consists of systemic corticosteroids, or budesonide, and azathioprine, to which most patients are initially responsive, although predictors of response are lacking. Relapses are very common, correlate with histological activity despite normal serum transaminases, and increase hepatic fibrosis. Furthermore, current regimens lead to adverse effects and reduced quality of life, whereas medication titration is imprecise. Biomarkers that can predict the clinical course of disease, identify patients at elevated risk for relapse, and improve monitoring and medication dosing beyond current practice would have high clinical value. Herein, we review novel candidate biomarkers in adult and pediatric AIH based on prespecified criteria, including gene expression profiles, proteins, metabolites, and immune cell phenotypes in different stages of AIH. We also discuss biomarkers relevant to AIH from other immune diseases. We conclude with proposed future directions in which biomarker implementation into clinical practice could lead to advances in personalized therapeutic management of AIH.
Clinical decision support in cardiovascular medicine
Authors: Yuan Lu, Edward R Melnick, Harlan M Krumholz
Journal: BMJ (2022)

Despite considerable progress in tackling cardiovascular disease over the past 50 years, many gaps in the quality of care for cardiovascular disease remain. Multiple missed opportunities have been identified at every step in the prevention and treatment of cardiovascular disease, such as failure to make risk factor modifications, failure to diagnose cardiovascular disease, and failure to use proper evidence based treatments. With the digital transformation of medicine and advances in health information technology, clinical decision support (CDS) tools offer promise to enhance the efficiency and effectiveness of delivery of cardiovascular care. However, to date, the promise of CDS delivering scalable and sustained value for patient care in clinical practice has not been realized. This article reviews the evidence on key emerging questions around the development, implementation, and regulation of CDS with a focus on cardiovascular disease. It first reviews evidence on the effectiveness of CDS on healthcare process and clinical outcomes related to cardiovascular disease and design features associated with CDS effectiveness. It then reviews the barriers encountered during implementation of CDS in cardiovascular care, with a focus on unintended consequences and strategies to promote successful implementation. Finally, it reviews the legal and regulatory environment of CDS with specific examples for cardiovascular disease.
Aseptic Abscess Syndrome With Ulcerative Colitis and Pyoderma Gangrenosum
Authors: Keiji Ozeki, Satoshi Tanida, Hiromi Kataoka
Journal: Clinical Gastroenterology and Hepatology (2022)

A 76-year-old female patient was admitted to our hospital with buttock pain, difficulty in walking, watery diarrhea, melena, abdominal pain, and skin eruption in the lower limbs. Computed tomography revealed abscesses in the right subgluteus maximus and right pectineus. Two weeks of broad-spectrum antibiotics were not effective. The abscesses were still apparent on magnetic resonance imaging acquired at 2 weeks after initiation of antibiotics (Figure A). A lower gastrointestinal endoscopy revealed left-sided ulcerative colitis (Figure B). The skin eruption was diagnosed as pyoderma gangrenosum based on neutrophil-dominant inflammation seen in tissue from skin biopsy (Figure C). No significant bacterial growth was detected in aspiration cultures from the abscess. The final diagnosis was aseptic abscess syndrome by exclusion diagnosis, and subsequent corticosteroid medication resulted in rapid clinical improvement, disappearance of both abscesses (Figure D), and no relapse following immunosuppressive therapy with azathioprine. If multiple deep organ abscess formations occur in patients with inflammatory bowel disease complicated by a neutrophil-induced eruption, regardless of the activity of intestinal lesions, a good prognosis can be obtained by the prompt use of immunosuppressive agents, such as corticosteroids, rather than antibiotics or surgery, with consideration to the possibility of aseptic abscess syndrome. Statement of confirmation: Informed consent was obtained from the patient for the publication of their information and imaging.
Waking up to monkeypox
Authors: Emmanuel Nakoune, Piero Olliaro
Journal: BMJ (2022)

In the past couple of weeks, the world has discovered monkeypox, an otherwise neglected infection caused by an orthopoxvirus related to the now eradicated smallpox.Monkeypox has been causing regular outbreaks in poorer, neglected communities in Central and West Africa, possibly with increasing frequency and geographic extent.
Intramural duodenal hematoma: an unusual complication after esophagogastroduodenoscopy in an adolescent
Authors: Paolo Cocco, Enrico La Pergola, Cosimo Bleve, Lorenzo Costa, Alessandro Brandolese, Nicola Schiavone, Salvatore Fabio Chiarenza
Journal: Endoscopy (2022)

Intramural duodenal hematoma (IDH) is a rare complication after small-bowel endoscopic biopsy; it occurs mainly in children with impaired coagulation [1] [2] [3] [4] [5]. We report the case of a 13-year-old girl with no relevant medical history who was complaining of abdominal tenderness and failure to thrive and underwent a diagnostic esophagogastroduodenoscopy (EGD) with duodenal biopsies ([Fig. 1]). After 24 hours, she presented with nonbloody, nonbilious vomiting, and diffuse and intense abdominal pain. Abdominal ultrasound and a contrast-enhanced computed tomography scan revealed an asymmetric thickening of the duodenal wall measuring 80 × 50 mm, suggestive of an IDH ([Fig. 2]). Laboratory testing showed that she had previously unknown platelet dysfunction. Only at this time did the family reveal details of an episode of hemarthrosis after minor trauma that they had previously omitted to mention.